Multimodality Imaging of Infective Endocarditis.

Infective endocarditis (IE) is a complex multisystemic disease resulting from infection of the endocardium, the prosthetic valves, or an implantable cardiac electronic device. The clinical presentation of patients with IE varies, ranging from acute and rapidly progressive symptoms to a more chronic disease onset. Because of its severe morbidity and mortality rates, it is necessary for radiologists to maintain a high degree of suspicion in evaluation of patients for IE. Modified Duke criteria are used to classify cases as "definite IE," "possible IE," or "rejected IE." However, these criteria are limited in characterizing definite IE in clinical practice. The use of advanced imaging techniques such as cardiac CT and nuclear imaging has increased the accuracy of these criteria and has allowed possible IE to be reclassified as definite IE in up to 90% of cases. Cardiac CT may be the best choice when there is high clinical suspicion for IE that has not been confirmed with other imaging techniques, in cases of IE and perivalvular involvement, and for preoperative treatment planning or excluding concomitant coronary artery disease. Nuclear imaging may have a complementary role in prosthetic IE. The main imaging findings in IE are classified according to the site of involvement as valvular (eg, abnormal growths [ie, "vegetations"], leaflet perforations, or pseudoaneurysms), perivalvular (eg, pseudoaneurysms, abscesses, fistulas, or prosthetic dehiscence), or extracardiac embolic phenomena. The differential diagnosis of IE includes evaluation for thrombus, pannus, nonbacterial thrombotic endocarditis, Lambl excrescences, papillary fibroelastoma, and caseous necrosis of the mitral valve. The location of the lesion relative to the surface of the valve, the presence of a stalk, and calcification or enhancement at contrast-enhanced imaging may offer useful clues for their differentiation. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

The Role of Platelets in Infective Endocarditis.

Over the last decade, the incidence of infective endocarditis (IE) has increased, with a change in the frequency of causative bacteria. Early evidence has substantially demonstrated the crucial role of bacterial interaction with human platelets, with no clear mechanistic characterization in the pathogenesis of IE. The pathogenesis of endocarditis is so complex and atypical that it is still unclear how and why certain bacterial species will induce the formation of vegetation. In this review, we will analyze the key role of platelets in the physiopathology of endocarditis and in the formation of vegetation, depending on the bacterial species. We provide a comprehensive outline of the involvement of platelets in the host immune response, investigate the latest developments in platelet therapy, and discuss prospective research avenues for solving the mechanistic enigma of bacteria-platelet interaction for preventive and curative medicine.

Cardiac Magnetic Resonance Imaging for the Diagnosis of Infective Endocarditis in the COVID-19 Era.

In the COVID-19 pandemic, to minimize aerosol-generating procedures, cardiac magnetic resonance imaging (CMR) was utilized at our institution as an alternative to transesophageal echocardiography (TEE) for diagnosing infective endocarditis (IE). This retrospective study evaluated the clinical utility of CMR for detecting IE among 14 patients growing typical microorganisms on blood cultures or meeting modified Duke Criteria. Seven cases were treated for IE. In 2 cases, CMR results were notable for possible leaflet vegetations and were clinically meaningful in guiding antibiotic therapy, obtaining further imaging, and/or pursuing surgical intervention. In 2 cases, vegetations were missed on CMR but detected on TEE. In 3 cases, CMR was non-diagnostic, but patients were treated empirically. There was no difference in antibiotic duration or outcomes over 1 year. CMR demonstrated mixed results in diagnosing valvular vegetations and guiding clinical decision-making. Further prospective controlled trials of CMR Vs TEE are warranted.

A Massive Number of Extracellular Tropheryma whipplei in Infective Endocarditis: A Case Report and Literature Review.

Whipple's disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei. If this bacterium presents an intracellular localization, associated with rare diseases and without pathognomonic signs, it is often subject to a misunderstanding of its physiopathology, often a misdiagnosis or simply an oversight. Here, we report the case of a patient treated for presumed rheumatoid arthritis. Recently, this patient presented to the hospital with infectious endocarditis. After surgery and histological analysis, we discovered the presence of T. whipplei. Electron microscopy allowed us to discover an atypical bacterial organization with a very large number of bacteria present in the extracellular medium in vegetation and valvular tissue. This atypical presentation we report here might be explained by the anti-inflammatory treatment administrated for our patient's initial diagnosis of rheumatoid arthritis.

Acute mitral valve regurgitation secondary to papillary muscle rupture due to infective endocarditis.

BACKGROUND: Papillary muscle rupture due to infective endocarditis is a rare event and proper management of this condition has not been described in the literature. Our case aims to shed light on treatment strategies for these patients using the current guidelines. CASE PRESENTATION: This case presents a 58-year-old male with acute heart failure secondary to papillary muscle rupture. He underwent an en bloc resection of his mitral valve with a bioprosthetic valve replacement. Specimen pathology later showed necrotic papillary muscle due to infective endocarditis. The patient was further treated with antibiotic therapy. He recovered well post-operatively and continued to do well after discharge. CONCLUSION: In patients who present with papillary muscle rupture secondary to infective endocarditis, clinical symptoms should drive the treatment strategy. Despite the etiology, early mitral valve surgery remains treatment of choice for patients who have papillary muscle rupture leading to acute heart failure. Culture-guided prolonged antibiotic treatment is vital in this category of patients, especially those who have a prosthetic valve implanted.

Post-treatment bacterial endocarditis mimicking fungal organisms: a morphologic comparison and tips for avoiding this diagnostic pitfall.

BACKGROUND: Histopathologic differentiation of bacterial endocarditis from yeast-like fungal endocarditis is usually straightforward; however, an underappreciated phenomenon is the effect of antimicrobial therapy on bacterial size, shape and septa (cross-wall) formation resulting in bacterial forms that mimic yeast-like fungi. In this article we illustrate the alterations that occur in antibiotic-treated Staphylococcus aureus endocarditis and compare these changes to histopathologic findings in unaltered S. aureus and Histoplasma endocarditis, respectively. METHODS: Resected valves from three cases of endocarditis were compared based on the type ofinflammatory reaction, organism morphology and culture results. Case 1 was S. aureus endocarditis initially misclassified as Histoplasma due to its atypical morphologic and histopathologic features. The two cases included for comparison were an S. aureus endocarditis with more classic features and an Histoplasma capsulatum endocarditis. Hematoxylin and eosin (H&E), Gram, periodic acid Schiff (PAS), Gomori-Grocott methenamine silver stains (GMS), and culture results were compared in all cases. Molecular and immunohistochemistry tests were used for confirmation of first case. High power oil-immersion was used to visualize organisms' characteristics in all three cases. RESULTS: Case 1 and Case 3 (Histoplasma-infected valves) had fibrinous exudates with scattered macrophages. The microorganisms observed in the first case of methicillin-sensitive S. aureus (MSSA) were ∼ 2-3 µm by GMS stain and had prominent septations. Histoplasma yeast were round to oval, ∼ 3-4 µm in size and demonstrated budding. S. aureus without alterations were round, ∼ 1 µm in size, and lacked prominent septations. Necrotizing purulent inflammation was present in the unaltered case of MSSA. The MSSA case with alterations from antibiotic treatment did not stain well with the Gram stain and organisms were best visualized with the PAS and GMS stains. CONCLUSIONS: Antibiotic therapy for bacterial endocarditis can alter the inflammatory reaction to infection, bacterial size, septa formation, and staining characteristics. Knowledge of these therapy-related effects and use of high-power magnification helps to avoid misclassification as yeast-like fungi.

Caries Experience and Knowledge About Oral Health Importance Among Children with Congenital Heart Diseases in Kosovo

Abstract Objective: To determine the dental health of children with Congenital Heart Diseases (CHD) and to evaluate the parents' knowledge of the importance of oral health and the risk of Bacterial Endocarditis. Material and Methods: This research included 140 children divided into the study group (80 children with CHD) and the control group (60 healthy children). The children were from different parts of Kosova, aged between 3-15. The parents were asked to complete a questionnaire containing demographic data (age and gender), general and special medical history (CHD types), knowledge about oral health importance and risk of bacterial endocarditis, and data about the daily oral hygiene child. The caries experience was reported using the DMFT/dmft index. Results: The average value of the dmft index was 6.7 for the study group and 5.62 for the control group, while the average value of DMFT index for the study group was 4.1, and for the control group was 3.47 (p>0.05). About 68.7% of parents of children with CHD were informed about their risk during dental interventions. However, knowledge was insufficient about the importance of oral health and dental prophylactic measures once only 32.7% of them were aware of those measures. Conclusion: No difference was observed between healthy and CHD children in caries experience and frequency of daily tooth brushing. Our findings provide evidence of a lack of knowledge about the importance of oral health and dental prophylactic measures among parents with CHD children (AU).

Novel human in vitro vegetation simulation model for infective endocarditis.

Infective endocarditis (IE) is a heart valve infection with high mortality rates. IE results from epithelial lesions, inducing sterile healing vegetations consisting of platelets, leucocytes, and fibrin that are susceptible for colonization by temporary bacteremia. Clinical testing of new treatments for IE is difficult and fast models sparse. The present study aimed at establishing an in vitro vegetation simulation IE model for fast screening of novel treatment strategies. A healing promoting platelet and leucocyte-rich fibrin patch was used to establish an IE organoid-like model by colonization with IE-associated bacterial isolates Staphylococcus aureus, Streptococcus spp (S. mitis group), and Enterococcus faecalis. The patch was subsequently exposed to tobramycin, ciprofloxacin, or penicillin. Bacterial colonization was evaluated by microscopy and quantitative bacteriology. We achieved stable bacterial colonization on the patch, comparable to clinical IE vegetations. Microscopy revealed uneven, biofilm-like colonization of the patch. The surface-associated bacteria displayed increased tolerance to antibiotics compared to planktonic bacteria. The present study succeeded in establishing an IE simulation model with the relevant pathogens S. aureus, S. mitis group, and E. faecalis. The findings indicate that the IE model mirrors the natural IE process and has the potential for fast screening of treatment candidates.

Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis.

Streptococcus gordonii and Streptococcus sanguinis are primary colonizers of tooth surfaces and are generally associated with oral health, but can also cause infective endocarditis (IE). These species express "Siglec-like" adhesins that bind sialylated glycans on host glycoproteins, which can aid the formation of infected platelet-fibrin thrombi (vegetations) on cardiac valve surfaces. We previously determined that the ability of S. gordonii to bind sialyl T-antigen (sTa) increased pathogenicity, relative to recognition of sialylated core 2 O-glycan structures, in an animal model of IE. However, it is unclear when and where the sTa structure is displayed, and which sTa-modified host factors promote valve colonization. In this study, we identified sialylated glycoproteins in the aortic valve vegetations and plasma of rat and rabbit models of this disease. Glycoproteins that display sTa vs. core 2 O-glycan structures were identified by using recombinant forms of the streptococcal Siglec-like adhesins for lectin blotting and affinity capture, and the O-linked glycans were profiled by mass spectrometry. Proteoglycan 4 (PRG4), also known as lubricin, was a major carrier of sTa in the infected vegetations. Moreover, plasma PRG4 levels were significantly higher in animals with damaged or infected valves, as compared with healthy animals. The combined results demonstrate that, in addition to platelet GPIbα, PRG4 is a highly sialylated mucin-like glycoprotein found in aortic valve vegetations and may contribute to the persistence of oral streptococci in this protected endovascular niche. Moreover, plasma PRG4 could serve as a biomarker for endocardial injury and infection.

Right-sided endocarditis caused by polyclonal Staphylococcus aureus infection.

We present a case of bacterial endocarditis with both methicillin-sensitive and methicillin-resistant Staphylococcus aureus, which based on typing, originated from two distinct clones. Such a case may be misinterpreted by microbiology lab automation to be a monoclonal multi-drug resistant Staphylococcus aureus, while simple microbiology techniques will instantly reveal distinct clonality.

A case report of endocarditis and spondylitis caused by Brucella melitensis biovar 3.

BACKGROUND: This case report describes the clinical process of a shepherd who suffered brucellosis-related endocarditis (BE) and spondylitis (BS) and was infected with Brucella melitensis biovar 3 (B. melitensis biovar 3). CASE PRESENTATION: A 55-year-old male patient was admitted to The First Affiliated Hospital of Shihezi University on October 11, 2018, due to over 3 months of intermittent fever, back pain, and heart trouble. The Rose Bengal Plate test was positive, the standard agglutination test titer for brucellosis was 1/800, and the blood culture was positive for B. melitensis biovar 3. Three instances of transthoracic echocardiography examination at days 1, 25, and 376 after admission to the hospital and magnetic resonance imaging (MRI) and computed tomography (CT) checks at days 5 and 38 revealed that the size of the vegetation on the posterior leaflet of the mitral valve increased from 0.7 × 1.4 cm to 1.2 × 1.5 cm and that the left atrium and ventricle were enlarged. The MRI and CT results showed hyperplasia of the second and third vertebra, a cold abscess formed on both sides of the psoas major muscles, and the vertebra hyperplasia became aggravated at a later time point. The patient's situation deteriorated, and heart failure was discovered on October 22, 2019. At the moment of submission of this manuscript, the patient remains in bed at home because of severe debility caused by brucellosis. CONCLUSIONS: This is the first reported case of endocarditis combined with spondylitis caused by B. melitensis biovar 3 in a shepherd. Brucellosis infection can cause work-power losses because of misdiagnosis or a lack of proper treatment. Early diagnosis and treatment are essential for a successful outcome.

Maltohexaose-indocyanine green (MH-ICG) for near infrared imaging of endocarditis.

Infectious endocarditis is a life-threatening disease, and diagnostics are urgently needed to accurately diagnose this disease especially in the case of prosthetic valve endocarditis. We show here that maltohexaose conjugated to indocyanine green (MH-ICG) can detect Staphylococcus aureus (S. aureus) infection in a rat model of infective endocarditis. The affinity of MH-ICG to S. aureus was determined and had a Km and Vmax of 5.4 µM and 3.0 X 10-6 µmol/minutes/108 CFU, respectively. MH-ICG had no detectable toxicity to mammalian cells at concentrations as high as 100 µM. The in vivo efficiency of MH-ICG in rats was evaluated using a right heart endocarditis model, and the accumulation of MH-ICG in the bacterial vegetations was 2.5 ± 0.2 times higher than that in the control left ventricular wall. The biological half-life of MH-ICG in healthy rats was 14.0 ± 1.3 minutes, and approximately 50% of injected MH-ICG was excreted into the feces after 24 hours. These data demonstrate that MH-ICG was internalized by bacteria with high specificity and that MH-ICG specifically accumulated in bacterial vegetations in a rat model of endocarditis. These results demonstrate the potential efficacy of this agent in the detection of infective endocarditis.

Isolated pulmonary valve endocarditis with rapid progression: a case report and literature review.

BACKGROUND: Isolated pulmonary valve endocarditis (IPE) is rare, accounting for 1.5-2% of all cases of infective endocarditis. Herein, we describe a case of isolated pulmonary valve endocarditis with rapid progression in a 28-year-old male. Unlike most patients reported previously who were cured with only anti-infective therapy, without surgery at an early stage, multiple complications occurred in this patient in less than 2 weeks. CASE PRESENTATION: The patient was diagnosed with pulmonary valve endocarditis with blood cultures showing Staphylococcus aureus and echocardiography revealing 2 masses (measuring 14*13 mm、11*16 mm in size). Only 12 days later, acute massive pulmonary embolism occurred. Then, repeated echocardiography revealed multiple masses attached to the pulmonary valve with severe pulmonary insufficiency and the possibility of pulmonary valve destruction. Finally, pulmonary valve replacement, vegetation removal, and right pulmonary thromboendarterectomy together with resection of the middle and lower lobes of the right lung were performed. CONCLUSIONS: The role of surgery at an early stage might need to be reconsidered, and it may be viable to combine medical and surgical approaches.

A novel sialic acid-binding adhesin present in multiple species contributes to the pathogenesis of Infective endocarditis.

Bacterial binding to platelets is a key step in the development of infective endocarditis (IE). Sialic acid, a common terminal carbohydrate on host glycans, is the major receptor for streptococci on platelets. So far, all defined interactions between streptococci and sialic acid on platelets are mediated by serine-rich repeat proteins (SRRPs). However, we identified Streptococcus oralis subsp. oralis IE-isolates that bind sialic acid but lack SRRPs. In addition to binding sialic acid, some SRRP- isolates also bind the cryptic receptor ß-1,4-linked galactose through a yet unknown mechanism. Using comparative genomics, we identified a novel sialic acid-binding adhesin, here named AsaA (associated with sialic acid adhesion A), present in IE-isolates lacking SRRPs. We demonstrated that S. oralis subsp. oralis AsaA is required for binding to platelets in a sialic acid-dependent manner. AsaA comprises a non-repeat region (NRR), consisting of a FIVAR/CBM and two Siglec-like and Unique domains, followed by 31 DUF1542 domains. When recombinantly expressed, Siglec-like and Unique domains competitively inhibited binding of S. oralis subsp. oralis and directly interacted with sialic acid on platelets. We further demonstrated that AsaA impacts the pathogenesis of S. oralis subsp. oralis in a rabbit model of IE. Additionally, we found AsaA orthologues in other IE-causing species and demonstrated that the NRR of AsaA from Gemella haemolysans blocked binding of S. oralis subsp. oralis, suggesting that AsaA contributes to the pathogenesis of multiple IE-causing species. Finally, our findings provide evidence that sialic acid is a key factor for bacterial-platelets interactions in a broader range of species than previously appreciated, highlighting its potential as a therapeutic target.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

Ultrastructure of a late-stage bacterial endocarditis valve vegetation.

Infective endocarditis (IE) remains a severe illness with high mortality rate, despite advances in antibiotic therapy and cardiac surgery. If infectious bacteria and platelets are two key players of human IE vegetation developmental process, their interactions and respective roles in fully developed late-stage IE vegetations remain obscure. The objective of this study was to better understand the organization of the different components of the IE vegetation and to provide a detailed description of this vegetation ultrastructure. A late stage Staphylococcal endocarditic vegetation was provided from a 13 years teenager patient. After reception of the surgical piece, we carried out a histological study using routine methods, notably the hematoxylin-eosin-saffron staining. Labeling with the anti-CD 61 antibody was also carried out. In a second step, we used transmission electron microscopy to describe the different regions making up the vegetation. Our ultrastructural study revealed vegetation was clearly composed by three different regions and identified the specific location of the bacteria and platelets in the vegetation tissues. Histological analysis showed that platelets and Staphylococcus aureus were not co-localized. Electron microscopy study confirmed that S. aureus were found at distance from platelets, as well from immune cells, embedded in a biofilm and/or a necrotic area. These results reveal a development of a deep bacteria-only niche in vegetation, raising questions about medication access to these microorganisms. Vegetation composed of three regions: a region rich in bacteria incorporated into the necrotic tissue, the second region composed of fibrin filaments and the third region rich in platelets and free of bacteria.